Anti-idiotypic antibodies of vascular endothelial growth factor and use thereof as drugs

Abstract

An anti-idiotypic vascular endothelial growth factor antibody, an Fab fragment, and pharmaceutical compositions thereof, being ligands of the human KDR receptor or of the murine flk-1 receptor and not a ligand of flt are provided.

1. Anti-idiotypic vascular endothelial growth factor antibody, said antibody being a ligand of the human KDR receptor or of the murine flk-1 receptor and not a ligand of flt. 
     
     
       2. Anti-idiotypic vascular endothelial growth factory antibody, having the following properties:
 a) it targets angiogenic endothelial cells,  
 b) it is circulating,  
 c) it has a half-life of about 23 days,  
 d) it induces phosphorylation on a tyrosine of a protein of 200 kDa,  
 e) it induces proliferation of vascular endothelial cells,  
 f) it does not induce migration of endothelial cells,  
 g) it stimulates angiogenesis,  
 h) it does not cause arterial hypotension, and  
 i) it does not affect the permeability of vessels.  
 
     
     
       3. Fab fragment of the anti-idiotypic antibody according to  claim 1 . 
     
     
       4. Fab fragment of the anti-idiotypic antibody according to  claim 2 . 
     
     
       5. Complex between an anti-idiotypic antibody according to  claim 1  and a toxin, or between an anti-idiotypic antibody according to  claim 1  and a radioactive element. 
     
     
       6. Anti-idiotypic antibody according to  claim 1  produced by the following steps:
 a) purified VEGF is injected into an animal,  
 b) blood is withdrawn to recover purified Ig containing specific anti-VEGF IgG, and then in an optional stage the specific anti-VEGF IgG are purified from the purified Ig,  
 c) said purified Ig or said purified anti-VEGF IgG are injected into an animal of the same origin as that used for injection of the VEGF,  
 d) blood is withdrawn to recover the total Ig, and then to subject the total Ig to two immunoadsorptions:  
 (i) an immunoadsorption on an affinity column prepared with the pre-immune Ig of the animal which has been used to produce the anti-VEGF IgG, to eliminate the anti-allotypic or isotypic antibodies,  
 (ii) an immunoadsorption on an affinity column prepared with the anti-VEGF IgG, to purify the anti-idiotypes.  
 
     
     
       7. Pharmaceutical composition, comprising an anti-idiotypic antibody according to  claim 1 . 
     
     
       8. Pharmaceutical composition, comprising an anti-idiotypic antibody according to  claim 2 . 
     
     
       9. Pharmaceutical composition, comprising the Fab fragment according to  claim 3 . 
     
     
       10. Pharmaceutical composition, comprising the complex according to  claim 5 .